DESCRIPTION (Taken directly from applicant's abstract) For over a decade investigation of basic mechanisms of inflammatory bowel disease (IBD) has been centered almost exclusively on the evaluation of local immune cells. This has considerably advanced our understanding of IBD pathogenesis, but other important systems have been overlooked. Although the cause of IBD is unknown, there is enough evidence to support the concept that inflammation does not result exclusively from immune cell abnormalities, also depending on the interaction of the latter with other "non immune" structural cells. Immune-non immune cell interactions are complex but represent a much more realistic approach to in vivo events than presently used experimental approaches. Addressing all possible cellular interactions in IBD would be overwhelming. This proposal will take a focused approach and evaluate the influence of two types of non immune cells, mesenchymal and endothelial cells on T lymphocytes. To investigate their interaction in a mechanistic fashion, we have developed unique cell systems that allow us to isolate, co-culture and study cell populations from normal and IBD-involved mucosa. These novel tools will be combined with molecular and immunological methods to test the following central hypothesis: The close physical and functional interaction of mesenchymal and endothelial cells with immune cells plays a key role in IBD by modulating mucosal immunity and inflammation. The specific aims are: 1) Characterization of immune and non immune cells from normal and IBD mucosa: 2) Evaluation of immune-non immune cell interactions in normal mucosa: 3) Assessment of immune-non immune cell interactions in IBD-involved mucosa. These aims will investigate mucosal immune events in health and inflammation in an integrated fashion. The cellular elements and experimental systems necessary to perform the proposed studies are available, have been tested and proved to be workable. We believe that this approach will generate enough new information to yield a fresh, more realistic look at basic regulatory events in normal and IBD-involved intestine.